5-141574114-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_005219.5(DIAPH1):c.1736G>A(p.Arg579His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005219.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.1736G>A | p.Arg579His | missense_variant | Exon 16 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.1709G>A | p.Arg570His | missense_variant | Exon 15 of 27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000647433.1 | c.1736G>A | p.Arg579His | missense_variant | Exon 16 of 29 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 178AN: 151930Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00109 AC: 271AN: 249466Hom.: 0 AF XY: 0.00113 AC XY: 153AN XY: 135352
GnomAD4 exome AF: 0.00143 AC: 2085AN: 1461840Hom.: 0 Cov.: 36 AF XY: 0.00136 AC XY: 992AN XY: 727216
GnomAD4 genome AF: 0.00117 AC: 178AN: 152048Hom.: 0 Cov.: 31 AF XY: 0.00124 AC XY: 92AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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DIAPH1: BP4 -
not specified Benign:1
p.Arg579His in exon 16 of DIAPH1: This variant is not expected to have clinical significance because it has been identified in 0.17% (210/126644) of European c hromosomes and in 0.28% (71/25790) of Finnish chromosomes by the Genome Aggregat ion Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs182139018). In addition, computational prediction tools and conservation analyses suggest that the p.Arg579His variant may not impact the protein. -
Autosomal dominant nonsyndromic hearing loss 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
DIAPH1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at